In this paper we obtain a one velocity macroscopic description of a mixture of two viscous compressible fluids by homogenization/averaging. The paper is written in two parts that can be read independently one of the other. In the first part, we propose two numerical schemes respectively for a two-fluid immiscible system, (i.e. two fluids separated by sharp interfaces) and for a bifluid mixture system (diffuse interface description via volume fractions). We present various simulations that suggest that the two systems of equations describe the same mixture at different scales and, as a consequence, that averaged velocity, density and pressure of the first model match with the respective velocity, density and pressure of the second model. In a second part, we show how to mathematically formalize the previous assertion via kinetic equations verified by the Young measures associated to oscillatory solutions of the model describing the finer scale.

The most common pancreatic diseases in cats are pancreatitis and exocrine pancreatic insufficiency (EPI). Non-invasive methods, such as serological quantification of feline pancreatic lipase immunoreactivity (fPLI), are often used in the diagnosis of pancreatitis. Previous studies have compared fPLI concentrations with histopathology, considered to be the gold standard for diagnosis of feline pancreatitis. However, fPLI concentrations in cats suffering from pancreatic tumours were rarely described. The aim of the present study was to determine the sensitivity and specificity of an in-house enzyme-linked immunosorbent assay (ELISA) for the quantification of fPLI in serum samples based on histopathological findings in cats diagnosed with various pancreatic diseases. Pancreatic biopsy samples from 80 cats were included. Five groups were defined on the basis of pancreatic histopathology: group 1, normal pancreas; group 2, nodular hyperplasia; group 3, mild pancreatitis; group 4, marked (moderate/severe) pancreatitis; and group 5, pancreatic neoplasia. Serum samples from all cats were tested by fPLI ELISA (<3.6 μg/l normal, 3.6–5.3 μg/l questionable, >5.3 μg/l pancreatitis). In group 1 (n = 19), serum fPLI values were within the reference interval in 74% of cases and in group 2 (n = 9) in 78%. Cats with mild pancreatitis (n = 23), marked pancreatitis (n = 11) and pancreatic neoplasms (n = 18) had significantly increased fPLI concentrations compared with group 1 (P = 0.004/0.001/≤0.0001). Cats with nodular hyperplasia had significantly lower fPLI values than cats with marked pancreatitis (P = 0.048) or tumours (P = 0.002). Serum fPLI concentrations in group 3 were <3.6 μg/l (n = 6), 3.6–5.3 μg/l (n = 4) and >5.3 μg/l (n = 13). Calculated test sensitivity for mild pancreatitis was fPLI >3.5 μg/l: 73.9% and fPLI >5.3 μg/l: 56.5%. In group 4 (n = 11), seven of nine cats (77.8%) with marked purulent pancreatitis had elevated fPLI. In group 4, a sensitivity of 81.8% was detected for fPLI >3.5 μg/l and 63.6% for fPLI >5.3 μg/l. Two cats with marked non-purulent pancreatitis had elevated fPLI, while two cats with marked purulent pancreatitis had normal fPLI values (<3.6 μg/l). In group 5, one cat with pancreatic adenoma and one with pancreatic acinar carcinoma had normal fPLI concentrations. The other cats with pancreatic adenoma (solid, n = 1; cystic, n = 4) or carcinoma (solid, n = 9; cystic, n = 2) had elevated or high fPLI values (4.1 to >40 μg/l, median 21.2 μg/l), probably caused by additional inflammation. The results of the present study confirm the importance of detailed histopathological characterization for the interpretation of clinical signs and fPLI values in feline pancreatitis. Primary pancreatic neoplasms may also lead to elevated fPLI concentrations as there is concurrent pancreatitis in most cases. However, severe pancreatic diseases, such as chronic non-purulent pancreatitis or tumours without inflammation, may result in normal fPLI values.

A 12-year-old, male mongrel dog was presented for a 6-month history of a progressive eyelid mass of the right upper eyelid. The dog's medical history reported long-term bilateral topical application of 0.03% tacrolimus ophthalmic ointment for third eyelid plasmoma and treatment cycles with systemic corticosteroids for a long-standing atopic dermatitis. Complete physical and ophthalmologic examination of the dog as well as complete blood count, serum biochemical analysis, urinalysis, thoracic radiographs, and abdominal ultrasonography were performed. The mass involved the skin and the margin of the upper eyelid, which was ulcerated. Conjunctival hyperemia, and the thickening and partial depigmentation of the third eyelid due to plasmoma were present. The plasmoma was observed bilaterally. Histological examination of the eyelid mass showed an invasive proliferation of malignant epithelial cells with intermixing of both adenocarcinomatous and malignant squamous cell components. An eyelid adenosquamous carcinoma was diagnosed. To the best of the authors’ knowledge, this is the first report on an adenosquamous carcinoma of the eyelid in a dog. Immunosuppression has been found to be a significant clinical risk factor for cutaneous adenosquamous carcinoma in humans and was considered a possible risk factor for this dog.

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Transitional cell carcinoma (TCC) is the most commonly diagnosed neoplasm in the urinary bladder. Distant metastases to the regional lymph nodes, lungs, abdominal organs or bones are noted in up to 50% of dogs at time of death. Surgical excision is often not practical as TCC typically involve the trigone of the bladder and/or occurs multifocally throughout the bladder with field cancerization. Therapeutic approaches are very challenging and the requirement to evaluate alternative therapeutic protocols that may prolong survival times in dogs bearing these tumours is compelling. We assessed the immunohistochemical expression of HER-2 in 23 cases of canine TCCs of the urinary bladder and compare it with non-neoplastic urothelium in order to evaluate a rationale for targeted therapies and gene-based vaccines. HER-2 positivity was recorded in 13/23 (56%) neoplastic lesions. The receptor was significantly overexpressed in neoplastic than in non-neoplastic samples (P = .015). According to our preliminary results, it would be of interest to further evaluate the role of HER-2 in canine TCCs as a marker of malignancy and a therapeutic target for cancer vaccine and antibodies. Moreover, the significantly different overexpression of HER-2 in TCCs than in non-neoplastic urothelium further supports to investigate its role in the progression toward malignancy of non-neoplastic lesions.

Case reportA 9-year-old male Bull Terrier was presented for a 3-month history of a progressive, non-painful conjunctival mass of the right eye. The mass was exophytic and located in the temporal bulbar conjunctiva. No adhesion to the sclera was detected. A presumptive clinical diagnosis of a conjunctival neoplasia was made. Complete physical and ophthalmological examinations of the dog, as well as complete blood count, serum biochemical analysis, urinalysis, thoracic radiography, echocardiography and abdominal ultrasonography, were performed. The mass was surgically removed and a double freeze-thaw cycle of cryotherapy was performed locally. Histological examination of the removed tissue showed a well-delineated, non-encapsulated mass composed of spindle cells in loose myxomatous stroma. No nuclear atypia was observed in the tumour cells. A positive Alcian blue stain confirmed the mucin origin of the stroma. Tumour cells stained positive on immunohistochemistry for vimentin and negative for cytokeratins. A diagnosis was made of conjunctival myxoma. No evidence of local recurrence or distant metastases was identified during the 24-month follow-up period.ConclusionTo the best of the authors' knowledge, this is the first report on a conjunctival myxoma in dogs.

Since the identification of cyclo-oxygenase-2 as a potentially important therapeutic target in veterinary oncology, numerous studies on its expression have been conducted. Unfortunately, results have been heterogeneous and conclusions are difficult to draw. We tested the ability of a defined positive control to guarantee reproducibility of results among different laboratories. Valid positive controls were defined by positivity of the renal macula densa without background labelling. Fifteen colorectal tumours and 15 oral squamous cell carcinomas were labelled immunohistochemically by six European laboratories. Slides were evaluated in blinded fashion for percentage of positive cells and labelling intensity by three pathologists, and results were analyzed statistically for reproducibility and inter-reader variability. Macula densa positivity was an insufficiently sensitive control to guarantee reproducible results for percentage of positive cells and labelling intensity. Inter-reader variability was proven statistically, making the case for image analysis or other automated quantitative evaluation techniques.

Overexpression of cyclo-oxygenase (COX)-2 is involved in tumour growth and spread by modulating the production of angiogenic factors such as vascular endothelial growth factor (VEGF). Expression of COX-2 and VEGF was investigated immunohistochemically in 51 canine and feline cutaneous and non-cutaneous squamous cell carcinomas (SCCs) and the correlation between expression of these molecules and clinicopathological variables was evaluated. COX-2 and VEGF expression was not observed in normal skin keratinocytes. COX-2 overexpression occurred in 53% and 61% of the canine and feline SCCs, respectively. The expression of both markers was higher in cutaneous compared with non-cutaneous SCCs. In both species COX-2 and VEGF expression was correlated with the progression of the disease, but not with the presence of lymphatic invasion, tumour grading or tumour classification in the cutaneous tumours. Further study will be required to understand the role of the COX-2 pathway in angiogenesis in SCC.

Prostaglandin (PG) signalling is involved in human and animal cancer development. PG E2 (PGE2 ) tumour-promoting activity has been confirmed and its production is controlled by Cyclooxygenase-2 (COX-2) and microsomal PGE synthase-1 (mPGES-1). Evidence suggests that mPGES-1 and COX-2 contribute to carcinogenesis through the EP2 receptor. The aim of our study was to detect by immunohistochemistry COX-2, mPGES-1 and EP2 receptor expression in canine (n = 46) and feline (n = 50) mammary tumours and in mammary non-neoplastic tissues. COX-2 positivity was observed in 83% canine and 81% feline mammary carcinomas, mPGES-1 in 75% canine and 66% feline mammary carcinomas and the EP2 receptor expression was observed in 89% canine and 54% feline carcinomas. The frequency of COX-2, EP2 receptor and mPGES-1 expression was significantly higher in carcinomas than in non-neoplastic tissues and adenomas. COX-2, mPGES-1 and EP2 receptor expression was strongly associated. These findings support a role of the COX-2/PGE2 pathway in the pathogenesis of these tumours.

Tissue microarray (TMA) is a high-throughput method adopted for simultaneous molecular profiling of tissue samples from large patient cohorts. The aim of this study was to validate the TMA method for the molecular classification of canine and feline mammary tumours. Twelve samples, five feline and five canine mammary tumours and two canine haemangiosarcomas, were collected. TMA construction was based on Kononen's method of extracting a cylindrical core of paraffin wax-embedded ‘donor’ tissue and inserting it into a ‘recipient’ wax block. Seven consecutive sections from each tissue array block were subjected to immunohistochemistry (IHC) using primary antibodies specific for oestrogen receptor (OR), progesterone receptor (PR), c-erbB-2, cytokeratin (CK) 5/6, CK14, CK19 and p63. The same panel of antibodies was applied to the full sections from all cases. Comparison between full sections and TMA scores revealed different results depending on the antibodies. Labelling for OR, PR, CK19 and p63 showed total concordance, c-erbB2 (score +2, +3) was concordant in nine out of ten cases, CK5/6 and CK14 in eight out of ten cases. The TMA platform preserves the molecular profile of canine and feline mammary tumour markers, representing a useful tool for rapid and cost-effective analysis for the first phenotypic screening using OR, PR and c-erbB2 antibodies. Basal cytokeratin, used for triple negative identification, shows a multifocal ‘niche’ expression pattern, for which IHC of the full section or multiple core array is recommended.

There is much interest in the potential use of selective inhibitors of cyclooxygenase (COX)-2 in combination with other cancer therapeutics. COX-2 is a key enzyme in prostaglandin synthesis and has been implicated in the pathogenesis of numerous canine and feline malignancies. There are few data on the potential role of COX-2 in the pathogenesis of canine lymphoma. The present study examined COX-2 expression in normal, hyperplastic and neoplastic canine lymphoid tissues. Immunohistochemical expression was evaluated in 12 samples of non-pathologically enlarged normal lymph nodes, 24 samples of hyperplastic lymph node and 44 samples of lymphoma (22 B-cell and 22 T-cell lymphomas). The labelling was scored semiquantitatively and a score of +2 or +3 was interpreted as overexpression. In hyperplastic lymph nodes only a few macrophages were COX-2-positive while six of the 44 lymphomas (13.6%; three B- and three T-cell lymphomas) overexpressed COX-2. These data provide a rationale for further investigation of COX-2 expression in canine lymphoma for prognostic, chemopreventive and chemotherapeutic purposes.

Distant metastases represent a major step in the progression and fatal outcome of canine and feline mammary carcinomas. Recent studies have characterized the molecular phenotypes of mammary tumours and provided information on molecules that may allow targeted therapy in sites from which the tumours may not readily be surgically resected. Molecular phenotypes were determined immunohistochemically in three feline and two canine cases of mammary neoplasia, each presenting with multiple distant metastases. These tumours and their metastases often overexpressed the c-erbB-2 phenotype. A basal-like phenotype was found in the distant metastases from two cases. These findings suggest that canine and feline mammary tumours with distant metastases may be amenable to novel targeted therapies.